ISSN(online): 2589-8698 ISSN(print): 2589-868X International Journal of Medical and Biomedical Studies

Available Online at www.ijmbs.info Volume 1, Issue 5; September-October: 2017; Page No. 07-15

Medicinal and therapeutically potential of Nigella Sativa Sandeep Gaur*, Bhavana Srivastava, Sanjay Gaur, Reena Bhardwaj, Renu Khanchandani 1Department of Pharmacology, Government Medical College & Hospital, Haldwani, Distt. Nainital, Uttarakhand, India.

ABSTRACT: Nigella sativa is a plant. People have used the seed to make medicine for over 2000 years. It was even discovered in the tomb of King Tut. Historically, black seed has been used for headache, toothache, nasal congestion, and intestinal worms. It has also been used for “pink eye” (conjunctivitis), pockets of infection (abscesses), and parasites. Today, black seed is used for treating digestive tract conditions including gas, colic, diarrhea, dysentery, constipation, and hemorrhoids. It is also used for respiratory conditions including asthma, allergies, cough, bronchitis, emphysema, flu, swine flu, and congestion. Other uses include lowering blood pressure, lowering cholesterol levels, treating cancer, and boosting the immune system. You may read that a patent has been issued to cover the use of black seed to improve immunity, but don’t be misled. The presence of a patent doesn’t mean black seed has been shown to be effective for this use. Women use black seed for birth control, to start menstruation, and to increase milk flow. Black seed is sometimes used in combination with cysteine, vitamin E, and saffron to ease the side effects of a chemotherapy drug called cisplatin. Some people apply black seed directly to the skin for joint pain (rheumatism), headache, and certain skin conditions. In foods, black seed is used as a flavoring or spice. There is some scientific evidence to suggest that black seed might help boost the immune system, fight cancer, prevent pregnancy, and lessen allergic reactions by acting as an antihistamine. For the improvement of human beings. Scientists, researchers should works to know more its other medicinal use in different diseases.

Key words: Nigella sativa, digestive tract, respiratory conditions, cancer, immune system.

INTRODUCTION: parts of Asia [1]. It is tiny and hairy being no more Nigella sativa is an annual herbaceous plant, than 3 mm in length, black seed originates from black seed (Nigella sativa) is believed to be the common fennel flower plant (Nigella sativa) indigenous to the Mediterranean region but now of the buttercup (Ranunculaceae) family. Nigella sativa is sometimes mistakenly confused with the found widely in india (like Jammu-Kashmir, [2] Himachal Pradesh, Bihar, Assam and Punjab). It fennel herb plant (Foeniculum vulgare) . The has been also cultivated into other parts of the plant has finely divided foliage and pale bluish world including Saudi Arabia, northern Africa and purple or white flowers. The flowers grow

Corresponding author: Sandeep Gaur 7

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terminally on its branches while the leaves grow Scientific Classification [7] opposite each other in pairs, on either side of the Kingdom: Plantae stem [3]. Its lower leaves are small and petiole (unranked): Angiosperms and the upper leaves are long (6-10 cm). The (unranked): Eudicots stalk of the plant reaches a height of twelve to Order: Ranunculales eighteen inches as its fruit, the black seed, Family: Ranunculaceae matures [4]. Genus: Nigella Nigella sativa reproduces with itself and forms a Species: Sativa fruit capsule which consists of many white Morphology: trigonal seeds. Once the fruit capsule has matured, it opens up and the seeds contained It is small prostrate annual herb about 45 cm within are exposed to the air, becoming black in high 2-3 slender leaves pinnatisect, 2-4 cm long [8] color (black seeds) [5]. Nigella sativa and its black cut into linear segment, segments oblong . seed are known by other names, varying Flowers pale, blue on solitary long peduncles, between places. Some call it black caraway; seeds trigonous and black in colour. The plant others call it black cumin (Kalonji), or even has a rather stiff, erect, branching stem, bears coriander seeds. In English, the Nigella sativa deeply-cut greyish-green leaves and [9] plant is commonly referred to as "Love in a terminal grayish blue flowers , followed by odd, Mist". Nevertheless, this is Nigella sativa, which toothed seed vessels, filled with small somewhat has been known and used from ancient times compressed seeds, usually three-cornered, with and is also known in Persian as Shonaiz [6]. two sides flat and one convex, black or brown externally white and oleaginous, strong agreeable aromatic odour, like that of nutmegs, and a spicy, pungent taste [10]. The flowers are delicate, and usuallycoloured pale blue and white, with 5–10 petals. The fruit is a large and inflated capsule composed of 3–7 united follicles, each containing numerous seeds. It has a pungent bitter taste and a faint smell of strawberries [11]. Etymology: Figure 1: Seeds of N.sativa The scientific name is a derivative of Latin niger (black).[12] The Common names are: In English, Nigella sativa seed is variously called fennel flower, nutmeg flower, black caraway, Roman coriander, and black cumin.[13] Other names used, sometimes misleadingly, are onion seed and black sesame, both of which are similar-looking, but unrelated. Blackseed and black caraway may also refer to Bunium persicum.[14] The seeds are frequently referred to as black cumin (as in Assamese: kaljeera or kolajeera or Bengali kalo jeeray), but black cumin (kala

jeera) is different from Nigella sativa (kali jeeri). Figure 2: Flower of N.sativa In Kannada, it is called Krishna jeerige, but this is 8

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also used for a different valuable remedy in treating gastrointestinal spice, Buniumpersicum[15]. It is used as part of dysfunction, and hepatitis and is described as a the spice mixture paanch phoran or panch stimulant to different conditions, high fever phoron (meaning a mixture of five spices) and by reliever[22]. itself in a great many recipes in Bengali cookery [16] Ibn Sina (980-1037), in his greatest "The Canon and most recognizably in naan bread . The of Medicine," regarded by many as the most çörek otu Turkish name literally means "bun's famous books in medicine, in the East or West, çörek herb" from its use in flavouring the buns. said the black seed as "stimulating the body's Such braided-dough buns are widespread in the energy and helps recovery from fatigue or lack of cuisines of Turkey and its neighbours spirit[23]. " Black seed is also included in the list of Tsoureki ( τσουρέκι). In Bosnian, the Turkish natural medicines Al-Tibb al-Nabawi, and N. sativa čurekot[17] name for is spelled as . The according to tradition, "Wearing black seed can seed is used in Bosnia, and particularly its capital cure all diseases except death." Prophetic somun Sarajevo, to flavour pastries (Bosnian: ) reference in describing black seed as "the healer often baked on Muslim religious holidays. of all diseases" are not too History of Nigella sativa: exaggerated exaggerated when it first Earliest written reference to black seed was first appeared. Previous studies have provided found in the book of Isaiah in the Old evidence indicating that the black seed has a real ability to improve the human immune system if Testament. Isaiah explains: "For the black cumin [24] is not threshed with a threshing Sledge, nor is a used all the time . Words of the Prophet "to cart wheel rolled over the cumin, but the black rely on the use of seed" also advocated for the cumin is beaten out with a stick, and the cumin use of seed consistently. with a rod [18]. Easton's Bible Dictionary explains Folk Medicine: that the Hebrew word for Black Cumin, "ketsah", Nigella sativa has been used for medicinal refers to "doubt the Nigella sativa, is the order purposes for centuries, both as a herb and Ranunculaceae which grows wild in pressed into oil, in Asia, Middle East, and Africa. Mediterranean countries, and cultivated in Egypt It has been traditionally used for a variety of and Syria [19]. conditions and treatments related to respiratory Dioscoredes, Greek physicist at unity century, health, stomach and intestinal health, kidney and reported that black seed is used to treat liver function, circulatory and immune system headaches, nasal congestion, toothache, and support, and for general well-being[25]. In Islam, it intestinal worms. In addition, also be used to is regarded as one of the greatest forms of promote menstruation and increase milk healing medicine available. The Islamic production in nursing mothers [20]. The Muslim prophet Muhammad once stated that the black scholar al-Biruni (973-1048), which combine seed can heal every disease except drugs ancestral India and China mentioned that death. Avicenna, most famous for his volumes Black seed is a kind of sesame seeds, called called The Canon of Medicine, refers alwanak in Sigzi dialect [21]. Later, this statement to Nigella as the seed that stimulates the body's is justified by the Suhar Bakht who explained energy and helps recovery from fatigue and that the black seed as habb-i-Sajzi (viz. Grains dispiritedness. It is also included in the list of Sigzi). Reference "grain" This allows people to natural drugs of 'Tibb-e-Nabavi', or "Medicine of use it as a nutritional ingredient in the 10th the Prophet (Muhammad)", according to the century and the 11th AD. In a medical system in tradition "hold onto the use of the black seeds Greco-Arab/Unani-Tibb, which originated from for healing all diseases. In theUnani Tibb system Hippocrates, Galen and Ibn Sina, black seed is a of medicine, N. sativa is regarded as a valuable

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remedy for a number of diseases [26]. The seeds Chemistry composition seeds of Nigella sativa: have been traditionally used in the Middle East Seeds of nigella contain numerous esters of and Southeast Asian countries to treat ailments structurally unusual unsaturated fatty acids including asthma, bronchitis, rheumatism and with terpene alcohols (7%); furthermore, traces related inflammatory diseases, to increase milk of alkaloids are found which belong to two production in nursing mothers, to promote different types: isochinoline alkaloids are [27]. Its digestion and to fight parasitic infections represented by nigellimin and nigellimin-N-oxide, oil has been used to treat skin conditions such andpyrazol alkaloids as eczema and boils and to treat cold include nigellidin and nigellicin. In the essential symptoms. Its many uses have oil (avr. 0.5%, max. 1.5%), thymoquinone was earned Nigella the Arabic approbation identified as the main component (up to 50%) 'Habbatul barakah', meaning the seed of besides p-cymene (40%), pinene (up to 15%), blessing[28]. Karayal seeds and their oil have a dithymo-quinone and thymohydroquinone. long history of folklore usage in Arabian and Other terpene derivatives were found only in Indian civilisation and are used in food as well as trace amounts:Carvacrol, carvone, limonene, 4- medicine. The seeds are used as flavouring, to [36] terpineol, citronellol . The essential oil improve digestion and produce warmth, contains significant (10%) amounts of fatty acid especially in cold climates. They are sometimes ethyl esters. On storage, thymoquinone yields scattered in the folds of woollen fabrics to dithymoquinonene and higher oligo [29, 30, 31]. preserve them from insect damage condensation products. The seeds also contain a In India the seeds are used as a carminative and fatty oil rich in unsaturated fatty acids, stimulant to mainly linoleicacid (50 60%), oleic acid ease bowel and indigestion problems and are (20%), eicodadienoic acid (3%) given to treat intestinal worms and nerve defects and dihomolinoleic acid (10%) [37].Saturated fatty to reduce flatulence, and induce sweating. Dried acids (palmitic, stearic acid) amount to about pods are sniffed to restore a lost sense of smell. 30% or less. Also contain parts of the essential It is also used to repel some insects, much oil, mostly thymoquinone, by which it acquires like mothballs. an aromatic flavor [38]. Traditional medicine: The seeds give on steam-distillation a yellowish In the Unani Tibb system of medicine, black brown volatile oil with an unpleasant odor. The cumin (Bunium bulbocastanum) is regarded as a oil contains carvone, d -limonene, and a carbonyl valuable remedy for a number of diseases compound, nigellone. [32]. In Islamic writing, a hadith narrated byAbu Nutritional value of Nigella sativa: Hurairah says "I heard Allah's Apostle saying, Black seed is rich in nutritional values. 'There is healing in black seed (haba sowda) for Monosaccharides (single molecule sugars) in the all diseases except death[33]. Nestlé has form of glucose, rhamnose, xylose, and reportedly filed a patent application covering use arabinose are found in the black seed. The black of N. sativa as a food allergy treatment.[34] Yet seed contains a non-starch polysaccharide the firm denies the claim of patenting the plant, component which is a useful source of dietary stating that the patent would only cover "the fiber. It is rich in fatty acids, particularly the specific way that thymoquinone - a compound unsaturated and essential fatty acids (Linoleic that can be extracted from the seed of the fennel [39] and Linoleic acid) . Essential fatty acids cannot flower - interacts with opioid receptors in the be manufactured by the body alone, and body and helps to reduce allergic reactions to therefore we acquire these from food. Fifteen [35]. food amino acids make up the protein content of the 10

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black seed, including eight of the nine essential Studies begun just over a decade ago suggest amino acids. Essential amino acids cannot be that if used on an ongoing basis, black seed can synthesized within our body in sufficient play an important role to enhance human quantities and are thus required from our diet. immunity, particularly in immunocompromise Black seed contains Arginine which is essential patients. [40]. Chemical analysis has for infant growth In 1986, Drs. El-Kadi and Kandil conducted a further revealed that the black seed contains study with human volunteers to test the carotene, which is converted by the liver into efficiency of black seed as a natural immune vitamin A, the vitamin known for its anti-cancer enhancer. The first group of volunteers received activity. The black seed is also a source of black seed capsules (1 gram twice daily) for four calcium, iron, sodium, and potassium. Required weeks and the second group were given a only in small amounts by the body, these placebo. A complete lymphocyte count carried elements' main function is to act as essential out in all volunteers before and four weeks after cofactors in various enzyme functions [41]. administration of black seed and the placebo Pharmacological action of Nigella sativa: revealed that the majority of subjects who took black seed displayed a 72% increase in helper to Antimicrobial activity: Nigella sativa exhibited strong antimicrobial activity suppresser T-cells ratio, as well as an increase in against Salmonella typhi, Pseudomonas natural killer cell functional activity. The control aeruginosa and others. The essential oil has been group who received the placebo experienced a shown to have activity against Gram-positive and net decline in ratio of 7%. They reported, "These Gram-negative bacteria [42]. However, sensitivity findings may be of great practical significance against Gram-positive bacteria such as Staphylo- since a natural immune enhancer like the black coccus aureus and Vibrio cholerae was found to seed could play an important role in the be stronger. Bacteria like Staphylococcus aureus, treatment of cancer, AIDS, and other disease S. pyog-enes and S. viridans are more susceptible conditions associated with immune deficiency to Nigella sativa. In an in-vitro study, volatile oil states." showed activity comparable to ampicillin[43]. The These results were confirmed by a study activity of the volatile oil also extended to drug- published in the Saudi Pharmaceutical Journal in 1993 by Dr. Basil Ali and his colleagues from the resistant strains of Shigella spp, [45,46] Vibrio cholerae and Escherichia coli and was College of Medicine at Kin Faisal University . found to have a synergistic action with In the field of AIDS research specifically, tests streptomycin andgentamycin. carried out by Dr. Haq on human volunteers at the Department of Biological and Medical Hepatoprotective activity: Research Center in Riyadh, Saudi Arabia (1997) Thymoquinone, one of the active constituents showed that black seed enhanced the ratio of Nigella sativa, is reported to have between helper T-cells and suppresser T-cells by hepatoprotective activity." An in-vitro study 55% with a 30% average enhancement of the showed the protective effect against tert-butyl natural killer (NK) cell activity. hydroperoxide (TBHP)-induced oxidative damage to hepatocytes. The activity was Anti-histamine activity: demonstrated by a decreased leakage of alanine Histamine is a substance released by bodily transaminase (ALT), aspartic transaminase (AST) tissues, sometimes creating allergic reactions and decreased trypan blue uptake[44]. and is associated with conditions such as bronchial asthma. Immune system strengthening: In 1960, scientists Badr-El-Din and Mahfouz found that dimer dithymoquinone isolated from 11

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black seed's volatile oil, under the name of the active principle was 100% effective in "Nigellone," and given by mouth to some preventing EAC tumor development. Results in patients suffering from bronchial asthma, mice who received DLA cells and black seed suppressed the symptoms of the condition in the showed that the active principle had inhibited majority of patients[47]. tumor development by 50% less compared to Following the results of this early study, mice not given the active principle. The study crystalline nigellone was administered to concluded, "It is evident that the active principle children and adults in the treatment of bronchial isolated from nigella sativa seeds is a potent anti- asthma with effective results and no sign of tumor agent, and the constituent long chain fatty [50]. toxicity. It was observed, however, that although acid may be the main active component effective, crystalline nigellone displayed a Anti diabetic activity: [48] delayed reaction . In 1993, Nirmal Significant hypoglycaemic activity has been Chakravarty, M.D., conducted a study to see if reported and is thought to be due to the this delay could be attributed to the possibility of essential oil present. Clinical studies have crystalline nigellone being an inhibitory agent on confirmed these results and suggest that histamine. His hypothesis proved correct. Dr. [5 the antidiabetic action of the plant extract Chakravarty's study found that the actual mechanism behind the suppressive effect of Anti inflammatory activity: crystalline nigellone on histamine is that Asthma and arthritis are chronic inflammatory crystalline nigellone inhibits protein kinase C, a disorders involving a variety of inflammatory substance known to trigger the release of mediators and different pathways. The fixed oil [49] histamine . In addition, his study showed that and thymoquinone from the seeds were found to crystalline nigellone decreased the uptake of inhibit eicosanoid generation in leucocytes and calcium in mast cells, which also inhibits membrane lipid peroxidation and a significant histamine release. reduction in rat paw edema and a reduction

The importance of these results are that people in granuloma pouch weight were also observed [52] who suffer from bronchial asthma and other . Nigella in low concentration is effective in allergic diseases may benefit from taking inhibiting the histamine release from the mast crystalline nigellone. cells, which supports an antiasthmatic role for the plant [52]. Anti-tumor activity: Antifertility activity: A study of black seed's potential anti-tumor principles by the Amala Research Center in The antfertility activity of Nigella sativa in male Amala Nagar, Kerala (India) in 1991 lent further rats has been established, shown by an inhibition impetus to Dr. Chakravarty's suggestion for the of spermatogenesis and a significant reduction possible use of black seed in the treatment of in sialic acid content of the testis, epididymis, [53] cancer.Using an active principle of fatty acids seminal vesicles and prostate . derived from black seed, studies with Swiss Antioxytocic activity: albino mice showed that this active principle could completely inhibit the development of a Preliminary reports common type of cancer cells called Ehrlich suggest antioxytocic properties, in that a ascites carcinoma (EAC). A second common type reversible inhibition of spontaneous smooth of cancer cells, Dalton's lymphoma ascites (DLA) muscle contraction and inhibition of uterine smooth muscle contraction induced cells were also used.Mice which had received the [54] EAC cells and black seed remained normal by oxytocin stimulation have been observed . without any tumor formation, illustrating that Cytotoxic activity: 12

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Cytotoxic and immunopotentiating effects in mind that natural products are not always of Nigella sativa have been established. The long necessarily safe and dosages can be important chain fatty acids are thought to contribute to [60]. Be sure to follow relevant directions on the antitumour activity. The extract shows product labels and consult your pharmacist or a modulatory effect in cisplatin-induced toxicity physician or other healthcare professional before in mice and a protective effect against cisplatin- using. induced falls in haemo-globin levels CONCLUSION: and leucocyte counts [55]. Nature gives us very valuable gifts in forms of Anthelmintic activity: plants, trees, herbs, shrubs etc. There are a lot Nigella sativa was found to have of plants and their products are very useful for an anthelmintic activity against tapeworm human beings. We use plants in many ways such comparable to that of piperazine[56]. as as for medicinal use.Herbs are the natural drugs used to regain the alterations made in Analgesic activity: normal physiological system by foreign The essential oil produced significant analgesic organisms or by any malfunctioning of the activity using chemical and thermal noxious body. The WHO has already recognized the stimuli methods such as acetic acid-induced contribution of traditional health care in tribal [57] writhing, hot plate and tail flick tests . communities. It is very essential to have a proper Promotes lactation: documentation of medicinal plants and to know their potential for the improvement of health A study by Agarwhal (1979) showed that black and hygiene through an eco friendly system. It is seed oil increases the milk output of very essential to know about a detailed and breastfeeding mothers. A literature search by the systematic study is required for identification, University of Potchefstroom (1989), including cataloguing and documentation of plants, which biological abstracts, revealed that black seed's may provide a meaningful way for the promotion capacity to increase the milk flow of nursing of the traditional knowledge of the herbal mothers could be attributed to a combination of medicinal plants. The present review shows that lipid portion and hormonal structures found in [58] black seeds have a lot of medicinal properties the black seed . and these medicinal properties are used for Other activites: treating many diseases. For the improvement of human beings. Scientists, researchers should Other reports include hypocholesterolaemic, works to know more its other medicinal use in antihyper-tensive and galac-ztagogue effects. different diseases. They should carry their research for develops its suitable formulation. Precautions and Adverse Reactions: [59] Which can be beneficial for humans as well as animals. No health hazards or side effects are known with the proper administration of designated REFERENCES: therapeutic dosages. 1. Zohary, Daniel, Hopf, Mari. Domestication of Black seed dosing: plants in the Old World Oxford University Press. 2000. The appropriate dose of black seed depends on 2. Ali BH, Blunden G. Pharmacological and several factors such as the user's age, health, and toxicological properties of Nigella sativa, several other conditions. At this time there is not Phytother Res.2003; 17(4): 299. enough scientific information to determine an 3. New_International_Encyclopedia appropriate range of doses for black seed. Keep

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4. Domestication of plants in the Old World (4 Orient Longman, Kottakal, India.1961;1:163- ed.). Oxford University Press. 2000. 72. 5. Andrews, F.W. The Flowering Plants of Anglo- 20. Rathee P.S, Mishra S.-H, and Kaushal R.Anti Egyptian Sudan; Arbroath, Scotland: 1952. microbial activity of essential oil, fixed oil and 6. Buckingham,J.(edit). Dictionary of Natural unsaponifiable matter of Nigella sativa L. Products, 1994; 7: 683. Indian J. Pharm Sci.1982; 44, 8-10. 7. Department of Biomedical Sciences, Zyed 21. Aqel M. Effects of Nigella sativa seeds on Complex for Herbal Research and Traditional intestinal smooth muscle. Int. J. Medicine, Unpublished results.2004. Pharmacogn.1993; 31:55-60. 8. Department of Pharmacognostic Sciences, 22. http://theblessedseed.blogspot.com/2012/0 Zyed Complex for Herbal Research and 1/for-energy-and-improved-immune- Traditional Medicine, Unpublished system.html results.2002. 23. Toama MA, Taha S El-Alfy and El-Fatatry HM, 9. Amin G.Popular Medicinal Plants of Iran. Antimicrobial Activity of the Volatile Oil of cytes and membrane lipid peroxidation. Nigella sativa Linneaus Seeds. Antimicrob Planta Med. Research Deputy of Health Agents Chemother, 1974; 6(2): 225-226. Ministry, Tehran, 1991; 61(1): 118-119. 24. Al-Hader A., Aqel M., and Hasan Z. 10. Mozaffarian V. A Dictionary of Iranian Hypoglycemic effects of the volatile oil of PlantsNames. Farhang Moaser Publishers, Nigella sativa. Int. J. Pharmacogn.193; 31: 96- Tehran, 1998; 6:365. 100. 11. Zargari A. Medicinal Plants, Vol. 1. Tehran 25. Hanafy M.S. and Hatem M.E. Studies on the University Press, Tehran, 1990; 1: 43-44. antimicrobial activity of Nigella sativa seed 12. http://www.naturalnews.com/026868_nigell (black cumin). J. Ethnopharmacol.1991; 34: a_sativa_migraine_seeds.html.(acesseson26/ 275-278. 12 /2013) 26. Department of Microbiology, Zayed Complex 13. http://www.naturalnews.com/038644_black for Herbal Research and Traditional _cumin_oil_immune_system_NK_cells.htm. Medicine, Unpublished results. (accesses on 12/01/2014) 27. http://www.prweb.com/releases/TMJ_relief/ 14. Randhawa MA and Al-Ghamdi MJ. A review migraine_prevention/prweb10440184.htm of pharmacotherapeutic effects of Nigella 28. http://www.drweil.com/drw/u/ART03106/Mi sativa, Pak J Med Res. 2002; 41(2):77-83. graine-Headaches.html 15. Ghazanfar,S.A. Handbook of Arabian 29. http://health.howstuffworks.com/diseasesco Medicinal Plants. Library of Congress.1994 nditions/headache/migraine3.htm 16. Hanafy MS, Hatem ME. Studies on the 30. Halwani R, Habbal MZ and Abdelnoor AM, antimicrobial activity of Nigella sativa seed The antibacterial effect of some constituents (black cumin. J Ethnopharmacol. 1991; 34(2- of Nigella sativa oil, Arab J Pharm Sci, 3):275-8. 1999;1(1): 87-96. 17. National Committee for Clinical Laboratory 31. Domestication of plants in the Old World (3 Standards, Performance standards for ed.). Oxford University Press. 2000. antimicrobial disc susceptibility testing; 32. Varghese E. SVD “Applied Ethnobotany- A Twelfth information supplement (M100-S12). case study among the Kharias of Central Wayne, PA: NCCLS, 2002. India”, Deep Publications, New Delhi. 1996 18. Kotb, T. F. Medicinal Plants in Libya. Arab 33. Adams R.-P. (1995), Identification of Encyclopedia House.Tripoli-Libya.1985. Essential Oil Components by Gas 19. Warrier,P.K. Nambiar,V.P.K. & Ramankutty Chromatography /Mass Spectroscopy. C.,Vaidya, Sala A. Indian Medicinal Plants Allured Publishing Co., Carol Stream.1995

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34. Chakravarty N. Inhibition of histamine 49. Dwivedi, Sumeet,Shrivastava, Satyaendra,Du release from mast cells by nigellone. Ann bey, Darshan; Kapoor, Shweta & Jain, Sanjay Allergy 1993; 70:237-42. “Status and conservation strategies of herbal 35. Daba MH, Abdel-Rahman MS. oral contraceptives”, Planta Indica, 2007; Hepatoprotective activity of thymoquinone in 3(1): 5-7. isolated rat hepatocytes. Toxicol Lett 1998; 50. Dwivedi SN, Herbal remedies 95:23-9. among tribals of sidhi district of Madhya 36. Mutabagani A. and El-Mahdy S.A.Study of the Pradesh, J. Econ.Tax. 2004;28(3) 675-686. anti-inflammatory activity of Nigella sativa L., 51. Akhtar MS, Riffat S. Field trial of Saussurea and thymoquinine in rats. Saudi Pharm. lappa roots against nematodes and Nigella J.1997; 5: 110- 113. sativa seeds against cestodes in children. J 37. Dehkordi FR, Kamkhah AF. Antihypertensive Pak Med Assoc 1991;41:185-7. effect of Nigella sativa seed extract in 52. A.G. and Peter A.C. (1998), The in vitro patients with mild hypertension. Fundam Clin antitumor activity of some crude and purified Pharmacol 2008; 22:447-52. components of black seed. Nigella sativa. 38. Dwivedi S et.al., Relivance of medicinal herbs Anticancer.1998;18:1527-1532. used in traditional system of 53. Houghton PJ, Zarka R, de las Heras B, Hoult medicine, Farmavita. Net, 2007. JR. Fixed oil of Black seed and derived 39. Kurion, J.C. “Plants that heals”, 5th ed. Pune, thymoquinone inhibit eicosanoid generation Oriental watchman publishing house, 2003. in leukocytes and membrane lipid 40. Nagi MN, Alam K, Badary OA, et al. peroxidation. Planta Med 1995; 61:33-6. Thymoquinone protects against carbon 54. Salem, M. L. and M. S. Hossain (2000). tetrachloride hepatotoxicity in mice via an Protective effect of black seed oilfrom Nigella antioxidant mechanism. Biochem Mol Biol Int sativa against murine cytomegalovirus 1999; 47:153-9. infection. International Journal of 41. Salomi NJ, Nair SC, Jayawardhanan KK, et al. Immunopharmacology.2000 Antitumour principles from Black seed seeds. 55. Salomi, N. J., S. C. Nair, et al. Antitumour Cancer Lett 1992; 63:41-6. principles from Nigella sativa seeds. Cancer 42. Worthen DR, Ghosheh OA, Crooks PA. The in Letters1992; 63(1): 41-46. vitro anti-tumor activity of some crude and 56. Khanna, T., F. A. Zaidi. CNS and analgesic purified components of blackseed, Black seed studies on Nigella sativa. Fitoterapia 1993; L. Anticancer Res 1998; 18(3A):1527-32. 64(5): 407-410. 43. Salomi NJ, Nair SC, Jayawardhanan KK, et al. 57. Kotb, T. F. Medicinal Plants in Libya. Arab Antitumour principles from Black seed seeds. Encyclopedia House.Tripoli-Libya.1985 Cancer Lett 1992; 63:41-6. 58. El, Dakhahny M. M. M., G. A. M. Abdel, 44. Aqel M. The relaxing effects of the volatile oil (1997). Prevention of skin tumors induced by of Nigella sativa seeds on vascular smooth 7,12-dimethylbenz anthracene in mice by muscles.1995 black seed oil. Oncology Reports,1997; 4(1): 45. Rittel & Reichstein, ibid., 1954;37: 1361 139-141. 46. Pendse & Dutt, Bull. Acad. Sci. Unit. Prov., 59. El-Dakhakhny M, Mady N, Lembert N, 1933; 34(3): 209. Ammon HP.The hypoglycemic effect of 47. http://www.divineremedies.com Nigella sativa oil is mediated by 48. http://www.uni- extrapancreatic actions. Planta Med.2002; graz.at/~katzer/engl/generic_frame.html?Nig 68(5): 465-6. e_sat.html.

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